ABSTRACT
Failure to thrive (FTT) is a term used to describe inadequate growth in infants. The immediate cause is undernutrition. Ghrelin is a potent orexigenic hormone that induces a positive energy balance and enhances appetite. There is no information regarding the possible role of ghrelin in infants with FTT. The aim of this study was 2-fold: 1) to examine circulating ghrelin levels in FTT infants, compared with those of normally growing infants; and 2) to evaluate appetitive behaviors in the two groups. Plasma acylated and total ghrelin concentrations were measured in nine FTT and five normally growing infants (age range, 9-18 mo). Appetite was assessed using three novel appetite measures. Both acylated and total ghrelin levels were significantly elevated in FTT infants compared with controls (p = 0.03 or less). Infants with FTT scored significantly lower than control infants on all appetite measures (p = 0.002 or less). Ghrelin levels were inversely related to appetite, weight velocity, weight/length z-scores, and weight z-score. These findings provide the first evidence that infants with FTT have higher circulating ghrelin concentrations but paradoxically lower appetite scores. Increased ghrelin secretion may reflect an adaptive mechanism attempting to increase appetite and preserve energy balance in response to poor nutritional state.
Subject(s)
Appetite , Child Development , Failure to Thrive/blood , Feeding Behavior , Ghrelin/blood , Infant Behavior , Protein Processing, Post-Translational , Acylation , Biomarkers/blood , Body Size , Body Weight , Case-Control Studies , Failure to Thrive/psychology , Female , Human Growth Hormone/blood , Humans , Infant , Insulin-Like Growth Factor I/metabolism , Male , Up-RegulationABSTRACT
It is established that dopamine inhibits while GABA stimulates LH release in goldfish. In this study, we examine dopaminergic regulation of GABAergic activity in the hypothalamus of early recrudescent female goldfish (Carassius auratus). We utilize a unique technique that permits concomitant quantification and correlation of in vivo GAD65 and GAD67 mRNA with GABA synthesis rate in response to decreased dopamine levels. Catecholamine depletion was achieved by treatment with alpha-methyl-para-tyrosine methyl ester (alphaMPT; 240 microg/g body weight), an inhibitor of tyrosine hydroxylase. Endogenous GABA levels were increased by intraperitoneal administration of gamma-vinyl GABA (GVG; 300 microg/g body weight), an inhibitor of the GABA catabolic enzyme GABA transaminase. Dual treatment of GVG+alphaMPT increased serum LH levels 4-fold. However, LH mRNA levels in the pituitary remained stable, suggesting that treatments affected secretion and not synthesis. In the hypothalamus, GABA synthesis rates increased 30% in response to alphaMPT treatment. This was correlated (r=0.61; p<0.05) to increased levels of GAD67 mRNAs but not GAD65 (r=0.14; p>0.05). These observations suggest that catecholamines inhibit GABA synthesis in the goldfish hypothalamus through isoform specific regulation of GAD67.
